INDIRECT EVIDENCE FOR NITRIC-OXIDE INVOLVEMENT IN MULTIPLE-SCLEROSIS BY CHARACTERIZATION OF CIRCULATING ANTIBODIES DIRECTED AGAINST CONJUGATED S-NITROSOCYSTEINE

Converging data suggest that nitric oxide (NO) production by cytokine- induced immune cells in demyelinating lesions is involved in multiple sclerosis (MS). High levels of NO may complex to suitable amino acids, causing an immune response against the formed neo-epitopes. By testin g MS sera with chemically defined nitroso-amino acids conjugated to ca rrier protein in ELISA, we observed a significant antibody reaction ag ainst the S-nitroso-cysteine epitope. The MS antibody response was exc lusively of LM isotype with an avidity of 8 x 10(-7) M. Sera of all cl inical MS forms showed a significantly elevated antibody titer versus sera from healthy subjects or from patients affected with other neurol ogical and autoimmune diseases. The detection of circulating antibodie s to a conjugated S-nitroso-cysteine epitope provides indirect evidenc e for NO involvement in MS.